DISCLAIMER: The cases / examples on this blog have been anonymised to maintain confidentiality of patients. Cases have been acquired from various international hospitals and through other medical colleagues with the intention to teach through case examples.

Monday, 16 March 2009

I hope you have had a good think about this case. It is difficult. I had no responses this month. To be honest, I am not surprised. Many very good physicians saw this patient and were unable to explain the variety of symptoms lacking physical signs, except pain, coupled with iron deficiency and absent inflammation.

It was only when an astute physician (Dr E.) decided to revisit the patient's history and with asking specific questions, did the possibility of this condition come to mind. The patient had been misdiagnosed variously with several other problems, given ineffective and inappropriate therapies.

When one has a difficult case such as this, it is best to stand back and look from afar. Remember the common conditions and put the rare diagnosis last, not first :-)

Question 2: What is your differential diagnosis given the thorough history and physical examination plus basic tests?

In this case, one needs to consider the common and then the less common differential diagnoses. As this patient is below the age of 50, we can consider the possibility of one single condition causing all the problems (Ockham's Razor) although we should still bear in mind Hickham's dictum i.e. the patient is allowed as many diagnoses as she likes.

Let us examine each main problem in turn.

Headache - this is a non-specific feature. The only clue to its potential origin is the fact that the patient wants to sleep in a dark room which is consistent with migraine. However, the pain is different from her previous migraines. This does not exclude migraine as the disorder can present in different ways over time. There are no associated auras of note. Again, this does not exclude migraine. Tension headaches should also be considered.

Waking with headache can be a feature of migraine although it makes one consider the problem of raised intracranial pressure. However, other features such as vomiting, visual disturbance are missing and moreover, the history is chronic rather than acute. One diagnosis in young women associated with headache and intracranial pressure is benign intracranial hypertension (pseudotumour cerebri). However, such a feature is not usually associated with the other manifestations noted by the patient.

We know this patient has a history of iron deficiency anaemia. Anaemia itself can cause headache as a non-specific feature, as is the case with many other symptoms in anaemia being non-specific.

The neurological examination is normal which gives us some confidence that a massive intracranial lesion is not present. Despite this, an intracerebral space occupying lesion (SOL) cannot be fully excluded by the physical examination. However, in view of the chronicity, lack of symptom change and the intermittency of the pain and lack of other CNS symptoms makes this diagnosis in an otherwise healthy young female less likely but not impossible.

Dizziness - this is an extremely common symptom. There are many causes. This patient has undergone the usual tests for investigating causes of the dizziness. Postural hypotension does not appear to be a feature here. Cardiac examination is unrevealing although from her family history, the mother has a dysrhythmia and hence, an inherited dysrhythmia cannot be excluded e.g. long QT syndrome, WPW etc. However, common things being common, anaemia itself can cause dizziness, as can migraines, HEENT problems, etc... One feature which is quite unusual is the feeling of dizziness when motionless. This brings one to consider migrainous vertigo which can occur when motionless (and which fits very nicely!) or whether there is a non-organic cause for the symptom such as anxiety or depression. One should always exclude organic causes first before labeling the patient with a potential psychiatric condition.

Mouth ulcers and odd eating habits - together suggest iron deficiency anaemia. Odd eating habits suggest the diagnosis of Pica. The iron deficiency is very likely to be due to menorrhagia (heavy menstrual bleeding) rather than a GI cause or poor nutrition. Despite the history of gastric cancer, this patient's recent gastroscopy and colonoscopy were entirely normal.

The chronic non-specific symptoms of excessive tiredness and sleepiness, poor concentration, myalgia, headaches etc suggest a multitude of different problems which include:

Infection

Bacterial: Lyme disease

Viral: Post-viral syndrome, HTLV, HIV

Endocrine:

Hypothyroidism (sometimes hyperthyroidism too!)

Hypoadrenalism

Reactive hypoglycaemia

Hyperparathyroidism

Cushing's syndrome

Connective Tissue Disease / Rheumatologic

SLE

Polymyositis

Mixed Connective Tissue Disease

Fibromyaglia

Behcet's disease

Sjogren's disease

Rheumatoid arthritis

Neoplastic

Leukaemia (unlikely as would have hopefully been identified on routine lab tests)

Lymphoma

Endometrial cancer with paraneoplastic syndrome

Insulinoma, pancreatic hyperplasia

Oncogenic osteomalacia

Metabolic / Toxic

Electrolyte disturbance (hyponatraemia, hypercalcemia etc; unlikely as these would have hopefully been identified on routine lab tests)

Lead poisoning (iron deficiency, headaches, poor concentration,

Chronic alcoholism ('closet alcoholic')

Psychiatric

Depression

Psychosomatic disorder

Munchhausen syndrome

Psychosis

Question 3: What additional test are required?

Common things are common. The history is extremely important here and should guide you in your lab testing. Try and avoid expensive tests that offer little extra information especially if the differential diagnoses you want to rule out are rare. Spending lots of money when you expect the test to come back negative is not the right way to do tests. This wastes time and money. It is better to test for the common things and if another disorder is still considered to be present after these initial results, then you can consider other tests at that point. Try and get out of the habit of ordering 'Panels' of expensive tests. Do not over test patients for the sake of doing tests. Rare diseases are rare.

I would test for thyroid and autoimmune disease initially. Without a history of travel within forested areas, testing for Lyme disease would not be on my initial list of tests. In view that the patient is sexually active, syphilis serology would be reasonable. An HIV test would be reasonable with patient consent. HTLV testing can be considered although it should be done depending on where the patient lives e.g. Southern Japan, Southeastern USA, would be risk areas.

A repeat gynaecological examination with transvaginal ultrasonography and endometrial biopsy would be reasonable to investigate and exclude malignancy.

ECG should be done to ensure there is no underlying dysrhythmia.

I would not routinely perform a CT head scan in this kind of patient. However, this is commonly done in some countries e.g. USA, Japan. Most patients presenting to their GP or hospital doctor in the UK would have a thorough history taken and a physical examination performed including fundoscopy. Unusual features of the above would be indicators for taking a head CT scan but otherwise the patient would be reassured and treated according to the likely cause. Urgent CT scanning should be reserved for patient with altered mental status, focal signs, and for any acute onset headache especially if associated with nausea and / or vomiting.

Question 4: What is your leading diagnosis?

The clue in this history is the non-specific tenderness in various sites throughout the patient's body. These locations fit for tendon insertion points. Hence, the likely diagnosis based on the diffuse mylagia, 'musculoskeletal-sounding' chest pain, poor concentration, tiredness, excessive sleepiness, headaches, dizziness etc are likely to be due to fibromyalgia!

I say this, rather than anaemia, because the anaemia resolved with iron sulfate giving a very reasonable haemoglobin level. Although this led to resolution of the anaemia, pica and mouth ulcers, it did not resolve other features suggesting that another condition was hiding beneath the surface. Hence, the iron deficiency although contributing to several non-specific symptoms was likely to be the 'red herring' hiding the true entity of fibromyalgia.

Follow-up results for this patient included the following:

Thyroid function was normal.

Autoimmune serology was within normal limits.

HIV and syphilis serology were negative.

Uterine ultrasonography was normal and endometrial histology was unrevealing.

Blood sugars were normal showing no extremes of high or low.

Blood smear showed no basophilic stippling. A formal lead level was never performed as it was thought unlikely that Pb-poisoning could have caused all these features.

ECG was normal.

Fibromyaglia

This is a diagnosis of exclusion. However, once other more sinister diagnoses have been ruled out, the diagnosis should be entertained. It is common! Some 3-10% of the general population are said to have the condition. Fibromyalgia and chronic fatigue syndrome have much overlap. Fibromyalgia generally affects women six times more than men occurring between the ages of 20-50 years with physical examination and laboratory findings being normal. The cause is not currently known although potential contributors include viral infections, depression, sleep disorder and aberrant perception of pain have been proposed.

Examination is normal except for pain in specific locations known as 'trigger points' as shown below: In order to satisfy the criteria for fibromyalgia, 11 tender trigger points must be present out of the total of 18.

A summary of the problems found in the condition is below:

Question 5: What is your treatment plan?

Treatment for fibromyalgia includes

Patient education - patients need to be informed that they do not have a serious medical condition and which is not progressive.

Drug Therapy: Antidepressant therapy has modest benefit e.g. fluoxetine (SSRI), amitryptilline (tricyclic agent). Less than half of all patient experience benefit from such therapy suggesting that not all cases involve depressive illness.

Exercise: Rather than resting up and taking it easy, patients should be encouraged to gradually increase their exercise tolerance by joining an exercise programme. In the UK, such exercise programmes can be prescribed on the NHS and are free for patients.

Fibromyalgia can take several years to be diagnosed. It may be misdiagnosed under the guise of several other conditions and hence, treated inappropriately. However, please try and keep this diagnosis in the back of your mind. Ultimately, it is the history and lack of physical signs that directs the physician to consider the diagnosis.

For further information please see any well respected evidence based text such as Harrison's, UpToDate etc...

Fibromyalgia is underdiagnosed and not well known about within the medical community. Please read the following from a Japanese patient who was diagnosed with it. It makes chilling reading - link.